Chemically Recyclable Poly(β-thioether ester)s Based on Rigid Spirocyclic Ketal Diols Derived from Citric Acid

Incorporating rigid cyclic acetal and ketal units into polymer structures is an important strategy toward recyclable high-performance materials from renewable resources. In the present work, citric acid, a widely used platform chemical derived from biomass, has been efficiently converted into di- and tricyclic diketones. Ketalization with glycerol or trimethylolpropane afforded rigid spirodiols, which were obtained as complex mixtures of isomers. After a comprehensive NMR analysis, the spirodiols were converted into the respective di(meth)acrylates and utilized in thiol–ene polymerizations in combination with different dithiols. The resulting poly(β-thioether ester ketal)s were thermally stable up to 300 °C and showed glass-transition temperatures in a range of −7 to 40 °C, depending on monomer composition. The polymers were stable in aqueous acids and bases, but in a mixture of 1 M aqueous HCl and acetone, the ketal functional groups were cleanly hydrolyzed, opening the pathway for potential chemical recycling of these materials. We envision that these novel bioderived spirodiols have a great potential to become valuable and versatile bio-based building blocks for several different kinds of polymer materials.

Alternative method using 2-MeTHF as solvent. tB (826 mg, 2.23 mmol) in a round bottom flask was dissolved in dry 2-MeTHF (30 mL). The flask was flushed with argon, capped with a rubber septum, and cooled down on an ice bath. Thereafter Et3N (0.81 mL) and acryloyl chloride (0.42 mL, 5.22 mmol, 2.25 eq) were added simultaneously dropwise. The ice bath was removed, and the mixture was stirred for 48 hours at room temperature. The completion of the reaction was estimated by TLC. The reaction was quenched by addition of saturated aq. NaHCO3 (50 mL) and extracted three times with EtOAc (3x 50 mL). The organic phases were combined, dried over MgSO4, and concentrated under the reduced pressure. The product was purified by flash chromatography over silica gel (30% EtOAc in petroleum ether). The pure product was obtained as an oily viscous liquid (825 mg, yield 77%) Synthesis of glycerol-spiro-diacrylate gBa gB (3.915 g, 13.67 mmol) was dissolved in dry CH2Cl2 (30 mL). The flask was capped with a rubber septum, flushed with argon, and cooled down using an ice bath. Acryloyl chloride (3.27 mL, 34.18 mmol, 2.4 eq) and Et3N (4.76 mL) were added simultaneously dropwise. The ice bath was removed, and the mixture was stirred overnight at room temperature. The reaction was quenched by addition of saturated aq. NaHCO3 (50 mL) and extracted three times with CH2Cl2 (3x 50 mL). The organic phases were combined, dried over MgSO4, and concentrated under reduced pressure. The mixture was purified by silica flash column (30% EtOAc in petrol ether). The pure product was obtained as an oily viscous liquid (3.219 g, yield 60%).

Polymerizations
The di(meth)acrylate (typically about 500 mg) was dissolved in CHCl3 (ca 100 mg/mL) and 1 equivalent of dithiol was added. The mixture was cooled on an ice bath and 0.1 equivalents of DBU was added as a solution in chloroform. The ice bath was removed shortly afterwards, and the mixture was stirred at room temperature for 24 hours. The polymer was then precipitated in 100 mL of MeOH and allowed to stir slowly overnight (16 h), after which the polymer had precipitated to the bottom. The solvent was decanted, and the polymer residue was left to dry for 5-10 minutes, after which a small amount of CH2Cl2 (2-3 mL) was added to solve the polymer for casting a film. The film was cast into a small Petri dish and left to dry at room temperature overnight, after which the film was removed from the dish for further drying under reduced pressure.

Polymerization of poly(tTa-HDT)
tTa (386.8 mg, 0.73 mmol) was dissolved in 5 mL of CHCl3, HDT (112.1 mg, 114 µl, 0.78 mmol) was added, and the mixture was cooled on an ice bath. DBU (11.9 mg, 0.078 mmol) was added as a solution in CHCl3, and the ice bath was removed. The mixture was stirred at room temperature for 24 hours. The mixture was then precipitated in 100 mL of MeOH while stirring slowly. The next day, the ether was decanted, the polymer residue solved in CH2Cl2 and cast into a Petri dish to obtain a thin film (373.5 g, yield 70.3%). 1  60 mmol) was dissolved in 10 mL of CHCl3, TBBT (670.8 mg, 2.67 mmol) was added, and the mixture was cooled on an ice bath. DBU (42.9 mg, 0.28 mmol) was added as a solution in CHCl3, and the ice bath was removed. The mixture was stirred at room temperature for 24 hours. The mixture was then precipitated in 100 mL of MeOH while stirring slowly. The next day, the ether was decanted, the polymer residue solved in CH2Cl2 and cast into a Petri dish to obtain a thin film (1.665 g, yield 76.7%). Some of the precipitate (170 mg) remained insoluble in CH2Cl2 and was collected separately. Alternative method in 2-Me-THF tTa (183.1 mg, 0.34 mmol) was dissolved in 6 mL of 2-MeTHF, TBBT (88.6 mg, 0.35 mmol) was added, and the mixture was cooled on an ice bath. DBU (5.6 mg, 0.03 mmol) was added as a solution in 2-MeTHF, and the ice bath was removed. The mixture was stirred at room temperature for 24 hours. Thereafter the mixture was then precipitated in 100 mL of MeOH while stirring slowly. The next day, the ether was decanted, the polymer residue solved in CH2Cl2 and cast into a Petri dish to obtain a thin film (110.1 mg, yield 38.4%). 1 (Fig. S27)

NMR analysis Glycerol spirodiol gB and diacrylate gBa NMR analysis
Ketalization of cis-bicyclo [3.3.0]octane-3,7-dione B with glycerol results in numerous isomers. At first the formation of 1,2 or 1,3 ketals is possible. In first case hydroxymethyl group can be connected to endo or exo position of C3 and C7 of cis-bicyclooctane ring and further isomers are obtained from the mutual different orientation of hydroxymethyl groups in diketals. 1 H NMR spectrum at 800 MHz is non-informative about the composition of mixture of compounds (Fig. S1). It is hard to resolve even numerous first order multiplets from 4-CH2OH substituted 1,3 dioxolane ring. For example, the number of signals from the vicinal couplings of H-4 between 4.00 and 3.95 ppm with neighbor methylene protons must be 128. 13 C NMR spectrum of ketalization product reveals the formation of complex mixture of compounds. For 13 C NMR spectrum the most informative starting points are the regions of spiro carbons with connected to them two carbon and two oxygen atoms. For the naming of these isomers generic names were used (see Fig. S2) In principle spiro connected to bicyclo[3.3.0]octane hydroxymethyl group at C4 of 1,3dioxolane ring can have 2 different configurations, but they are barely observed due to low barrier conformational mobility of 1,3-dioxolane ring. Geometry optimizations by AM1 and Gaussian calculations show that these isomers differ in their energies in the order of only 100 cal/mol and have in most stable conformation diversely twisted bicyclo[3.3.0]octane 5membered rings which are characterized also by the different dihedral angles between the bicyclo[3.3.0]octane bridgehead H atoms. Different calculations give these angles values from nearly zero to more than 30 degrees. The 1,3-dioxolane parts of isomers are characterized by a low inversion barrier of conversion from the different mutual orientation of substituents on the 1,3-dioxolane ring. No NMR study of this conversion was found, but an ESR study from 1973 has found that the inversion barrier in 2-methyl 1,3-dioxolane is as low as 5.6±0.2 kcal/mol 1 . This needs temperatures below -100 °C degrees to observe different conformers in NMR spectra. Room temperature linewidths in present mixture are quite narrow to resolve 0.003 ppm differences in 13 C chemical shifts, but at the same time they already demonstrate the small exchange broadening effects. This is seen in the 13 C spectrum of bicyclo[3.3.0]octane bridgehead carbons in a mixture of glycerol di-and monoketals at room temperature (Fig. S4). Resolution enhancement reveals the presence of dynamic broadening in signals from diketals. The monoketal itself is also not free from the exchange effects, because the keto ring signals are even sharper compared to the other monoketal signals. The number of observed isomers led to the conclusion that mutual orientation of substituents in 1,3-dioxolane ring isomers are still separable in NMR spectra. Additionally, exo and endo substitution cis and trans orientations of hydroxymethyl substituents were observed. For further analysis the configuration of one hydroxymethyl group was fixed and remaining substitution patterns were fixed toward this substituent. The analysis of 6 isomeric diketals was based on NMR spectra of glycerol monoketals and 2,2-dimethyl-1,3-dioxolan-4-yl-methanol (solketal, Fig. S3) 13 C NMR spectrum of monoketals shows the presence of 2 compounds defined as exo and endo isomers with the chemical shift differences between the corresponding atoms from 0.01 to 0.5 ppm. The largest difference is observed on methylene groups of 1,3-dioxolane ring due to their exo or endo orientation on bicyclo[3.3.0] ring in beta position from spiro carbon. As a model compound for the assignment of exo or endo methylene groups the chemical shifts of 3methoxy isomers of cis-bicyclooctane derivatives were used 2 . In this study endo methoxy carbons on C3 of bicyclooctane were shifted to low field. The same regularity is observed also for 1,3-dioxolane ring methine carbon atoms in present isomers. Further confirmation of assignment of exo or endo configuration of hydroxymethyl substituents follows from 1 H chemical shift differences of bicyclo[3.3.0]octane bridgehead proton chemical shifts, which result from long range deshielding effects of CH2OH groups in exo isomers by shifting bridgehead protons to low fields by about 0.02 ppm. Very small 1 H chemical shift differences in two monoketal isomers complicate the use of NOESY experiments for the analysis of interactions between the spiro and bicyclooctane ring protons in these isomers. Another model compound, solketal behaves differently from the 2-methyl-1,4dioxaspiro [4.5]decane with 4-methylsubstituted 1,3-dioxolane ring. For the last compound half chair conformation was declared on the basis of vicinal H-H spin-spin coupling constants with methine proton as 5.7 and 8.4 Hz 3 . In solketal and in present monoketal and diketals these coupling constants have very similar values (in solketal 6.5 and 6.6 Hz in CDCl3 and 6.3 and 6.4 Hz in DMSO, in both monoketals 6.7 and 6.3 Hz in CDCl3 and 6.5 and 6.1 Hz in DMSO). These results justify the use of solketal as adequate model for the analysis of present isomers. Methyl atoms on C2 of solketal have different 1 H and 13 C chemical shifts. These chemical shifts were assigned by NOESY experiments, which show that both proton and carbon chemical shifts are for methyl groups cis oriented to hydroxymethyl group shifted towards low fields. This result is in accordance with 13 C NMR studies of stereoisomeric 2,4-dialkyl 1,3dioxolanes 4 . Full assignment of 13 C chemical shifts in monoketals was achieved by 13 C-13 C INADEQUATE correlation experiments. This results in assignment of connections between the bridgehead and methylene carbons of bicyclo[3.3.0]octane ring, which are important for the assignment of cis and trans isomers of unsymmetrical endo-exo isomers. Correlations between the bridgehead carbons were not observed due to too low intensities of outer signals of AB spin systems. With the information from solketal and monoketals the diketal mixture was analyzed by various 2D FT experiments (COSY, NOESY, HSQ, HMBC, SELECTIVE HMBC, INADEQUATE). Spectra were measured in CDCl3, MeOD and DMSO-d6. Best resolution of bicyclo[3.3.0]octane bridgehead protons was observed in DMSO solution (Fig. S1), being complex band of overlapping signals, but still giving possibility to assign by 2D FT bridgehead 10 carbon signals to definite isomers (Fig. S4). INADEQUATE experiment was used to sort out signals to all isomers. In Fig. S5 the connectivity diagram of bridgehead carbons is demonstrated and in Fig. S6 the assignment of methylene carbon atoms in 6 isomers is shown. Acrylic acid diesters from the mixture of spirodiols have retained the same relative concentrations of 6 the isomers. Expanded 13 C NMR spectrum is quite similar to the spectrum of diols (Fig. S7). In 13 C typical NMR esterification effects are observed in alcohol parts of isomers where in alpha position regular ~2 ppm low field and in beta position ~3 ppm high field shifts are registered. At more remote positions different types of carbon atoms are shifted marginally to higher fields. Terminal acrylic carbons are not now any more separated to 8 components and carbonyl carbons show 2 signals representing only exo and endo orientation towards bicycle C3 and C7. Esterification of spirodiols results in smaller variations of carbon chemical shifts within bicyclo[3.3.0]octane bridgehead carbon chemical shifts. In diester they occupy less than 0.30 ppm, in spirodiols they have 0.50 ppm range. The most surprising result in 1 H NMR is the resolution of vinyl protons to 6 from possible 8 types. In Fig. S8 1 H signals from high field half of terminal Z-vinyl protons with only geminal 1.4 Hz coupling constants are shown. These chemical shift differences are result of 22 bond distance between the terminal vinyl H atoms in these isomeric acrylic acid diesters. Fig. S1. Room temperature 800 MHz 1 H NMR spectrum from isomeric dispirodiols mixture in DMSO solution 5

.3.3]propellane spirodiol tT NMR analysis
1 H spectrum of tT points to dynamic effects in the molecule. Two bands from carbocyclic sixmembered ring protons at 1.4 ppm (Fig. S11) are not unresolved equatorial and axial protons, but they are result of intramolecular exchange process. This exchange is even better seen in 13 C spectrum (Fig. S10) from the observed linewidths, where signals from all 5 rings of these molecules are influenced. Linewidths in this spectrum reflect the chemical shift differences in exchanging positions of molecules. They are smallest in quaternary carbons resulting in their opposite to normal most intensive signal intensities. In reported NMR data for unsubstituted [4.3.3]propellane 2 singlet signals with intensity ratio 2 to 3 at 1.40 and 1.58 ppm were reported for 1 H at 80 MHz and assigned 13 C chemical shifts fit with present data of isomeric propellanes except needed obvious exchange of assignment of six membered ring C2, C5 and five membered rings methylene groups signals. Nothing was reported about intramolecular exchange processes for [4.3.3]propellane. The simplest model compound for dynamics study should be 1,1,2,2-tetramethyl cyclohexane, but data for inversion barrier in this compound were not available. For 1,1-dimethyl cyclohexane experimental NMR studies have reported for ΔG of 10.2 5 and 10.5 6 kcal/mol. These values are very close to reported values on unsubstituted cyclohexane. 7 Thus the observed exchange broadening is specific to present isomers. Our NMR probehead was not suitable for low temperature experiments where temperatures lower than -50 °C are needed. AM1 calculations show that trans isomer is more stable by 90 cal/mol and in both isomers the dihedral angle at bridgehead in 6-membered carbocycle is 36.6 degrees. In NMR spectra all methylene protons with 14.4 Hz geminal spin-spin coupling constants in 5-membered rings resonate within 0.07 ppm. For methylene carbons this interval is nearly 100 times larger, demonstrating the advantages of 13 C NMR spectroscopy in stereochemical studies.